It is important to understand the cellular and molecular biology of lung tissue to increase our understanding of the respiratory disease processes and to develop effective methods for prevention, diagnosis and therapy of lung diseases. Appropriate models to achieve these goals must be developed. The use of in vitro activated alveolar macrophage (AM) systems to study the immunological and biochemical events related to AM microbicidal activity offers a unique approach to study lung defense and increase our understanding of AM function. This proposal is concerned with the development of an animal model of in vitro activated AM microbicidal activity. The use of this model to obtain specific information concerning (a) the role of T and B lymphocytes on activation of AM, (b) the effects of local and systemic immune responses on the activating lymphocytes, and (c) the relationship of activation- associated metabolism and phagocytosis-associated metabolism to AM microbicidal activity. Specifically, a previously described model of in vitro activated peritoneal macrophages will be adapted to the AM. By selectively triggering either T or B lymphocytes, the role of each in AM activation can be determined. By using either lymph node cells involved in local immune response or spleen cells involved in a systemic immune response, the effect of the type of immune response on the lymphocyte in AM activation can be determined. By comparing AM metabolism in the presence and absence of activating factors, or particles, activation- associated or phagocytosis-associated metabolism, respectively, can be identified. Use of appropriate metabolic inhibitors can then be used to determine the relationships of activation- and/or phagocytosis- associated metabolism to intracellular microbicidal activity. Such a characterized model would have future application in comparative studies of the AM in disease.